Nutrition and cancer Flashcards
What is the leading cause of death in developed countries?
cancer
What is the main risk factor for cancer?
Age Other big factors include environmental factors, including diet
Nutritional factors may contribute to about __% of tumors
Nutritional factors may contribute to about 30% of tumors
What is cancer?
uncontrolled growth of abnormal cells in the body
characteristics of cancerous cells
– Escape normal growth signals
– Can replicate indefinitely, can form tumors
– Can avoid programmed cell death (apoptosis)
– Can alter energy metabolism
– Can avoid immune surveillance
– Can invade other tissues (metastasis)
– Can develop a blood supply (angiogenesis)
Synonyms of carcinoma
malignant tumors, neoplasms, carcinoma
What are benign tumors?
not cancerous, do not invade and metastasize
What is the first stage of cancer formation?
the process starts with alteration of the gene
DNA is altered
can be from virus, radiation, chemicals
this leads to initiation cell with damaged DNA
Do cancers develop 100% of the time when cell’s DNA is altered/intiation cell is created?
we all have some initiated cells, but we also have defences against replication of such cells
defences can be deactivated and cells will differentiate
What are the changes that occur, leading to development of intiatied cell?
- Activation of protooncogenes
- Inactivation of tunour-suppressor genes
- Inactivation of genoic stability genese
- Defects in growth control
- Defects in terminal differentiation
- Resistance to cytotoxicity
- Defects in programmed cell death
What are the 3 steps of cancer development?
- Initiation
- Promotion
- Progression
What are the factors that can affects the way genotype is expressed in the phenotype?
Penetrance
Epigenetics
Define mutation
What are the possible sources?
structural change in the base pair sequence of DNA
Sources:
– Inherited: eg. BRCA1 gene ↑ risk of breast and ovarian cancer
– Due to exogenous factors e.g. radiation, chemicala, viruses
What is penetrance
Penetrance in genetics is the proportion of individuals carrying a particular variant (or allele) of a gene (the genotype) that also express an associated trait (the phenotype).
What role can SNPs play in cancer?
Single nucleotide polymorphisms (SNP): may affect the response to exposures
What is the most common type of polymorphisms?
SNPs
Polymorphisms vs mutations
Polymorphisms are weaker but more common than mutations
What do Epigenetic changes affect?
affect gene structure, function and expression
What are the common types of epigenetic changes?
– DNA methylation (hypermethylation of the promotor region of tumor suppressor genes → silencing)
– Acetylation of the histones → affects chromatin folding
Nutritional genomics and proteomics =
interactions between diet and genes and their products
diet inclued bioactive components such as __ but also __
diet inclued bioactive components such as nutirents but also non-nutrients
What is the largest effect on genes of a diet?
the largest effect being on epigenetics and translation to mRNA and protein
as well as post-translation impact that affect structure and function of protein
How can bioactive food components affect genes?
How can food increase and decrease oxidative damage to DNA?
– Increased by carcinogens found in foods, polyunsaturated fatty acids, iron
– Decreased by antioxidant nutrients (Vit C & E ) or cofactors in antioxidant enzymes (selenium, copper)
Folate and DNA link
Direct role of folate in DNA synthesis, repair and methylation
Aspects of the cell cycle that can be affected by bioactive food components
Possible causes of cancer
diet and obesity combined-> 1/3 of effects
diet-> 10-20%
• It is estimated that nearly 1 in _ Canadians will be diagnosed with cancer in their lifetime.
• It is estimated that nearly 1 in 2 Canadians will be diagnosed with cancer in their lifetime.
How has the number of cancer cases diagnosed each year has been changing?
The number of cancer cases diagnosed each year has been increasing because of the growing and aging population. When the effect of age and population size are removed, the risk of cancer has been decreasing.
Most common types of cancers in males and females
Males: prostate, lungs, colorectal
Females: breast, lungs, colorectal
Is inicidence/mortality higher in males or females
both are higher in males
What is the deadliest type of cancer? Why?
lung cancer is the deadliest cancer in both sexes
it is because this type is typically diagnosed late
no specific treatment
Cancer ourcomes and incidence in relation to age
Older people are more likely to be diagnosed with cancer and are more likely to die
Trends in cancer mortality
mortality has decreased significantly
cancer is now seen as a chronic disease
Why is lung cancer related mortality and incidence decreasign?
lung cancer mortality and incidence is decreasing due to public health measure of anti-smoking
Trends by cancer type in male population
Trends by cancer type in female population
Most common types of cancer for 0-14 yo
Leukemia
CNS
Lymphoma
Most common types of cancer for 15-29 yo
Thryoid
Testis
Hodgkin lymphoma
Which provinces in Canada have the highest cancer death and incidence?
- Nunawut- has low incidence and high mortality, this is due to less access to medical care
- Newfoundland
- Nova Scotia
Are cancer rates higher in developed or underdeveloped countries?
Higher cancer rates are seen more in developed countries-> proves that cancer is majorly dependent on environmental reasons (diet, smoking, lack of activity, obesity, lack of exercise)
Cancer incidence in developed vs. developing countries
Developing countries: oesophagus, liver
liver cancer rates have to do with infections by hepatitis in developing countries
stomach cancer is caused by food toxins (e.g afflotoxins in grains and cereal) in developing countries
Design of studies addressing diet and cancer (4 types)
Limitations of studies addressing diet and cancer
Which method is often used to collect dietaty intake data? Why?
FFQ → represent usual diet over long periods, adequate for large populations
Are biochemical markers of nutrients useful in research?
Biochemical indicators may be useful for some nutrients (serum oxidative markers, 25(OH)D, …) but not for others (total fat, fiber, sodium, retinol…)
How is systematic reviews and meta-analysis limited?
→ limited by possibility of selective publication of positive results (publication bias), difficulty in combining dietary data and control of covariates.
Summary of Recommendations American Cancer Society
- Achieve and maintain a healthy weight throughout life
- Be physically active
- Eat a healthy diet, with an emphasis on plant foods
- Choose foods and drinks in amounts that help you get to and maintain
- Limit how much processed meat and red meat you eat
- Eat at least 2.5 cups of vegetables and fruits each day
- Choose whole grains instead of refined grain products
- If you drink alcohol, limit your intake
- Drink no more than 1 drink per day for women or 2 per day for men.
Obesity and cancer risk
- higher prevalence of certain cancer in obese people- breast, uterus, colon and kidney
- to some extent: gallbladder, pancreas
- lung cancer patients are typically thin as they were smokers, but now there are more obese clients
- obese women have higher risk of breast cancer as the adipose tissue acts as the source of estradiol
How is energy balance related to cancer?
The rate of cell division is influenced by energy balance and growth rates → could ↑ replication of initiated cells
How is excess weight connected to cancer mortality
Excess weight contribute 14% to 20% of all cancer mortality in the US
Mechanism of obesity and increased cancer risk
- Levels and metabolism of hormones (e.g. insulin, estradiol )and growth factors (IGF-1)
- obese women have higher risk of breast cancer as the adipose tissue acts as the source of estradiol hyperinsulinemia linked to obesity (insulin acts as a growth factor) promotes cancer growth
- Effects on inflammation and immune function
- ↑reflux-> ↑risk of esophagus cancer
- more reflux in obese people
What is the impact of energy restiction on cancer
Energy restriction reduces development of cancer in experimental models
– The most consistent and strongest effect of diet in animal studies
– Pioneer studies in the 1950s: ↓30% energy intake=↓90%mammary tumors
How is weigt loss, insulin and cancer connected?
Modestweightlossimprovesinsulinsensitivityandhormone metabolism, thus leading to decreased cancer risk
Dietary fat and cancer
- Several animal studies showed that diets high in fat promote tumor growth, but dependent on total energy intake
- Large international differences in breast, colon, endometrium, prostate CA correlate with animal fat intake per capita.
- fat itself is not linked to cancer, its connection is due to the caloric value (if its excessive)
But
- In breast and colon CA
– Pooled analyses of prospective studies showed no association – Intervention trials of low-fat diet → do not support a benefit
– no support of an association with fat (either poly, mono or saturated) that is independent from energy intake
- thus the type of fat doesn’t matter
Cancer and sugar
- As for excess fat, excess sugar may indirectly increase cancer risk by promoting excess weight
- Suger increases energy intake without providing any of the nutrients that reduce cancer risk (empty calories)
- Refined sugar = brown sugar = honey = maple syrup in terms of calories
- Recommendation: limit food and beverages of low nutritional value
For breast, colon, endomethium and prostate, benefits of exercise are __ effects on body weight
For breast, colon, endomethium and prostate, benefits of exercise are independent from effects on body weight
Consume a healthy diet, with an emphasis on __
Consume a healthy diet, with an emphasis on plant foods
Dietary patterns that are connected wiht higher/lower cancer risk
– Individuals who eat more processed and red meat, potatoes, refined grains, and sugar-sweetened beverages and foods are at a higher risk of developing certain cancers
– whereas a diet that contains a variety of vegetables and fruits,whole grains, and fish or poultry or that is lower in red and processed meats is associated with a lower risk
Patterns do not indicate which component is more important
Healthy dietary patterns are associated with decreased risk of _
Healthy dietary patterns are associated with decreased risk of cancer, CVD and all cause mortality.
What is the type of cancer associated with hihg intake of red and processed meat?
associations with colorectal CA
– From meta-analysis: 12-17% increase in (probable) risk of colon CA with 100g -increment of red meat intake daily;
49% increased risk (convincing) with 25 g-increment of processed meat daily
Potential mechanism of red meat and cancer
– Preservatives (nitrites + salt) -> nitrosamines (known carcinogens)
– Cooking at high temperature e.g. frying, broiling, grilling → polycyclic aromatic hydrocarbons and heterocyclic amines (known carcinogens)
– Heme promotes the formation of N-nitroso compounds (nitrosamine)
– Animal fat? May promote formation of secondary bile acids
Overall recomendation for read meat and cancer?
Red meat is nutrient dense>recommend not every day, limit portion size and mode of cooking that avoids charring
Why are fruits and veggies reccomended?
– contain vitamins, minerals, fibres and many phytochemicals with potential anti carcinogenic properties (carotenoids, terpenes, sterols, indoles, phenols)
– Diet rich in F&V may help maintaining healthy weight
– recent large prospective studies found weak associations with lung, upper
GI and colorectal CA, and inconsistent with other CA
Some promising veggie-nutrient specific associations
– Lycopene-containing foods and prostate CA
– Cruciferous vegetables and several CA sites
– Allium vegetables and stomach CA
– Folate-rich F&V and colon CA
B-carotene, Vit C and E, selenium supplement benefits
potential roles in reducing cancer risk through antioxidant properties by neutralizing reactive oxygen species (ROS) that cause DNA damage.
But, epidemiological studies and intervention trials have shown no benefits of providing these isolated nutrients in supplements
Select trial outcomes
Se+ vit E supplements (SELECT trial): no effect on prostate CA, perhaps ↑ risk
Are anti-oxidant supplements recommended?
Antioxydant supplements not recommended; consume whole foods
Why choose whole grain instead of refined?
Sources of fibres, vitamins and minerals
Proposed mechanisms of fibres and lower GI cancers:
– dilute or bind potential carcinogens, limit contact with mucosa by speeding transit, alter colonic flora, reduce pH, serve as substrate to flora producing short-chain fatty acids, e.g. butyrate which has anti-proliferative effect.
Case-control vs short-term study results about fiber
Case-control studies initially supported the protective hypothesis but short-term intervention studies did not
Recent dose-response meta-analysis of prospective studies on fiber conclusions
– dietary fiber intake was inversely associated with colon CA risk
– Panel conclusion: dietary fibers probably protects against colon `CA
Fiber may also contributed to reduce cancer risk of other CA through __
Fiber may also contributed to reduce cancer risk of other CA through maintenance of healthy weight
How is alcohol and cancer related
Known cause of CA of the oral cavity, pharynx, larynx, esophagus, and liver, especially when combined to cigarette smoking- synergetic effect
– Proposed mechanism: direct contact and toxicity in the liver
Which cancer risk is increased by alcohol?
– Breast CA: 10-12% higher risk with each drink/day
– Colon CA: 40% higher risk with 3drinks/day
Proposed mechanism of alcohol elevating cancer risk
– Production of acetaldehyde-> DNA damage
– For breast CA, alcohol may increase estrogens levels
-> total intake is important, not type of alcohol
Dairy products and cancer
- high milk and dairy consumption is associated with↓ risk of colon CA (also benefits from calcium supplements, possibly vitamin D) (level of evidence = probable)
- Some studies suggested an association between dairy product intake and ↑ risk of prostate CA (also see calcium), but recent dose-response meta- analysis showed no association for non-advanced, advanced and fatal prostate CA.
calcium and cancer
Vit D and cancer
level of evidence: convincing
- decreased risk
- increased risk
level of evidence: probable
- decreased risk
- increased risk
For whcih diet elements is research still ongoing?
vitamin D, turmeric and other spices
Limited-suggestive level of evidence
- decreased risk
- increased risk
Limited-no conclusion level of evidence
- decreased risk
- increased risk
